22-42920661-A-G

Variant names:

• chr22-42920661-A-G
• rs7364152
• NM_001184970.3:c.-77-8504T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001184970.3(PACSIN2):​c.-77-8504T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.673 in 151,952 control chromosomes in the GnomAD database, including 36,707 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.67 (36707 hom., cov: 30)
• Consequence: PACSIN2 NM_001184970.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.87
• Publications: 7 publications found

Genes affected

PACSIN2 (HGNC:8571): (protein kinase C and casein kinase substrate in neurons 2) This gene is a member of the protein kinase C and casein kinase substrate in neurons family. The encoded protein is involved in linking the actin cytoskeleton with vesicle formation by regulating tubulin polymerization. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2010]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.908 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001184970.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PACSIN2	NM_001184970.3	MANE Select	c.-77-8504T>C		intron	N/A	NP_001171899.1
	PACSIN2	NM_001349969.2		c.-77-8504T>C		intron	N/A	NP_001336898.1
	PACSIN2	NM_001349970.2		c.-77-8504T>C		intron	N/A	NP_001336899.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PACSIN2	ENST00000263246.8	TSL:1 MANE Select	c.-77-8504T>C		intron	N/A	ENSP00000263246.3
	PACSIN2	ENST00000403744.7	TSL:1	c.-77-8504T>C		intron	N/A	ENSP00000385372.3
	PACSIN2	ENST00000407585.5	TSL:1	c.-77-8504T>C		intron	N/A	ENSP00000385952.1

Frequencies

GnomAD3 genomes AF: 0.673 AC: 102138 AN: 151834 Hom.: 36664 Cov.: 30

Gnomad AFR AF: 0.915

Gnomad AMI AF: 0.510

Gnomad AMR AF: 0.738

Gnomad ASJ AF: 0.535

Gnomad EAS AF: 0.822

Gnomad SAS AF: 0.610

Gnomad FIN AF: 0.455

Gnomad MID AF: 0.566

Gnomad NFE AF: 0.547

Gnomad OTH AF: 0.667

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.673 AC: 102234 AN: 151952 Hom.: 36707 Cov.: 30 AF XY: 0.672 AC XY: 49910 AN XY: 74252

African (AFR) AF: 0.916 AC: 37974 AN: 41474

American (AMR) AF: 0.738 AC: 11259 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.535 AC: 1857 AN: 3470

East Asian (EAS) AF: 0.821 AC: 4245 AN: 5170

South Asian (SAS) AF: 0.609 AC: 2934 AN: 4816

European-Finnish (FIN) AF: 0.455 AC: 4787 AN: 10518

Middle Eastern (MID) AF: 0.561 AC: 165 AN: 294

European-Non Finnish (NFE) AF: 0.547 AC: 37151 AN: 67936

Other (OTH) AF: 0.663 AC: 1398 AN: 2108

Alfa AF: 0.626 Hom.: 5484

Bravo AF: 0.706

Asia WGS AF: 0.719 AC: 2502 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.20
DANN	Benign	0.57
PhyloP100		-1.9
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7364152; hg19: chr22-43316667;